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Biomedical subjects

J B Cannata-Andía

Publications and source records attributed to J B Cannata-Andía.

16 recordsLinked to original sources

Prevalence of osteoporosis in men and determinants of changes in bone mass in a non-selected Spanish population.

Osteoporotic studies conducted exclusively in men have been limited by the discrepancies in defining densitometric osteoporosis and, also, because osteoporosis has traditionally been associated only with women. The aims of this study were to describe the prevalence of low bone mineral density (BMD) and osteoporotic fractures as well as the rate of bone loss. The analysis of some risk factors for accelerated bone loss was also evaluated. Men aged 50 years and over, randomly selected from the Oviedo municipal register (n = 308), completed a questionnaire regarding risk factors related to osteoporosis; they underwent two lateral radiographs of the dorsal and lumbar spine and a dual X-ray absorptiometry (DXA) study at the lumbar spine and hip. In the 4th year of the follow-up period, participants were invited to undergo repeats of the same tests that had been carried out in the initial study. The prevalence of densitometric osteoporosis in men older than 50 years, standardized by age, was 8.1% with regard to at least one of the four studied bone areas, with a slight increase with age. The prevalence of osteoporotic fracture, standardized by age, was 24.4%, with a marked increase with age. Osteoporotic prevalent fracture was independently associated only with the rate of change in lumbar spine BMD. From all the osteoporotic risk factors analyzed, only low milk consumption and regular smoking were independently associated with loss of bone mass. In summary, prevalent osteoporotic fracture was independently associated with the rate of change in the lumbar spine BMD but not in the other segments studied. Avoiding smoking and ensuring an adequate milk intake might prevent the loss of bone mass in men.

Absorptiometry, Photon↗

The effect of vertebral fracture as a risk factor for osteoporotic fracture and mortality in a Spanish population.

There is little data concerning the morbidity, mortality, and epidemiology of vertebral fracture. The aim of this study was to evaluate the effect of prevalent and incident vertebral fractures as risk factors for further osteoporotic fractures and mortality. The study was performed on a cohort of 316 women and 308 men older than 50 belonging to the EVOS study, randomly selected from our city register. At the beginning of the study and 4 years later, lateral dorsal and lumbar X-rays were performed. In addition, evaluation of the incidence of osteoporotic nonvertebral fractures was performed throughout 8 years. The incidence of all osteoporotic fractures was higher in women than in men (two-fold increase in vertebral fracture incidence and five-fold increase in Colles' and femur incidence). Vertebral fracture was a strong risk factor for a new vertebral fracture [RR=4.7 (1.8-11.9)], hip fracture [RR=6.7 (2.0-22.7)] and Colles' fracture [RR=3.0 (1.1-7.8)]. Prevalent and incident vertebral fractures were associated with a higher risk of having a hip fracture [RR=10.0 (2.0-50.2)] and Colles' fracture [RR=5.5 (1.3-23.4)]. In addition, in women, the vertebral fracture was associated with a higher mortality. By contrast, no association was found in men. These results demonstrate the association between a previous vertebral fracture with increments in the incidence of osteoporotic fractures of any type. In addition, we found a significantly higher mortality rate in women having vertebral fractures. These findings support the necessity of preventing the occurrence of vertebral fractures to limit their strong negative impact on mortality.

Aged↗

Hormonal replacement therapy in an animal model with chronic renal failure and ovariectomy: biochemical and densitometric study.

BACKGROUND: In spite of estrogen replacement therapy being extensively used in clinical and experimental studies without renal impairment, there are no long-term studies concerning estrogen replacement in chronic renal failure. METHODS: In this experimental study, six groups of nephrectomized and ovariectomized animals were treated with different doses of 17beta-estradiol, alone or in combination with calcitriol, to evaluate the effect of these treatments on bone metabolism. RESULTS: Biochemical results showed that estrogen alone did not have any effect neither on calcium nor on PTH serum levels. By contrast, in the groups treated with calcitriol, the levels of serum calcium were significantly higher, and the levels of iPTH were significantly lower than those observed in the control group. Animals receiving the combined treatment with estrogen and calcitriol showed the greater gain in uterus weight and a better bone mineral density at the lumbar site and the proximal and distal tibia sites. CONCLUSION: The combination of estrogen and calcitriol is the most effective therapy to prevent bone mass loss in animals with chronic renal failure and estrogen deprivation.

Absorptiometry, Photon↗

A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms.

A novel missense activating mutation in the extracellular calcium-sensing receptor (CaSR) is reported in this work. It was identified in three related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). The proband, a 27-year-old woman, diagnosed as having hypoparathyroidism at 7 years of age and a history of seizures, showed the highest penetrance of the mutation. The remaining two affected members presented asymptomatic chronic hypocalcemia despite severe hypoparathyroidism associated with high levels of serum phosphate and calcium urinary excretion. The missense mutation (Glu(604)Lys) affected an amino acid residue in the C terminus of the cysteine-rich domain of the extracellular amino-terminal domain, which seems to be required for the coupling of ligand binding to the activation of intracellular signaling pathways. This genetic change cosegregated with hypocalcemia in all the individuals where the mutation was found. As parathyroid hormone (PTH) secretion is the regulatory target of the CaSR, polymorphism analysis of the PTH gene was carried out. PTH polymorphisms were analyzed in the kindred studied. Affected members for the Glu(604)Lys CaSR mutation which also carried the uncommon PTH alleles showed higher penetrance of the mutation, with more severe autosomal dominant hypocalcemia. These results suggested that the PTH gene could act as a modifier locus of ADH, affecting the penetrance of the activating CaSR mutation described.

Adolescent↗

Reference values for trace and ultratrace elements in human serum determined by double-focusing ICP-MS.

Reference values for trace and ultratrace elements concentrations in healthy human serum, measured by double-focusing inductively coupled plasma-mass spectrometry (ICP-MS), are presented. Blood donors from Asturias (Spain) were selected as the reference population (n=59). Blood samples were collected, after donation, taking the necessary precautions to avoid contamination. All subjects analyzed had normal renal function and nutritional status, as shown from their creatinine and albumin levels. A total number of 14 elements (Al, Ca, Cr, Mn, Fe, Co, Cu, Zn, Rb, Sr, Mo, Cd, Pb, and U) were monitored almost simultaneously. Serum samples were diluted 1+4 with ultrapure water and matrix interferences were corrected using Sc, Ga, Y, and Tl as internal standards. Fe, Cu, and Zn were also determined by isotope dilution analysis (IDA). Reference trace element concentrations intervals observed containing 95% of the reference distribution after excluding outliers are presented. Fourteen serum samples from hemodialysis patients were also analyzed for comparison. High levels of Al, Cr, Sr, Mo, Mn, Pb, U, Co, and Cu and low levels of Fe, Zn, and Rb were found in the serum samples from hemodialysis patients compared to the corresponding reference values observed in this work.

Adult↗

Bone aluminum uptake in uremic rats receiving intraperitoneal iron.

To assess the effect of concomitant iron and aluminum loads on bone aluminum accumulation and on the response to the deferoxamine test in rats with the same aluminum surcharge, Wistar rats with chronic renal failure were divided into three groups: iron-overloaded rats (N = 6) (intraperitoneal iron); iron-depleted rats (N = 6) (blood withdrawal two to three times per week); control rats (N = 4) (no manipulation). All groups received intraperitoneal aluminum simultaneously. After 6 wk, a deferoxamine challenge test was performed. Thereafter, bone aluminum and iron were measured. The iron-overloaded rats showed higher bone iron content (iron overloaded: 147.7+/-55.4 microg/g; iron depleted: 7.9+/-1.0, and controls 13.3+/-9.9 microg/g, p < 0.010) and lower bone aluminum content (iron overloaded: 14.2+/-4.0 microg/g; iron depleted: 70.9+/-35.1 microg/g; controls: 72.7+/-28.3 microg/g p < 0.005). No differences were found between the iron-depleted and control rats. After the deferoxamine infusion, the iron-depleted rats tended to have higher serum aluminum increments (p = NS) and higher urinary aluminum excretion (p < 0.012, p < 0.020) than control rats despite similar amounts of aluminum in bone of the two groups. Aluminum bone accumulation was minor if iron and aluminum loads were given concomitantly. The iron depletion influenced the results of the deferoxamine challenge test in rats with similar bone aluminum burden.

Aluminum↗

Use of ultrafiltration and chromatography to assess aluminum speciation in serum after deferoxamine administration.

Deferoxamine effectively chelates aluminum by forming aluminoxamine, a low-molecular-weight compound removable by dialysis. However, aluminum-bound species other than aluminoxamine might be present in serum after the administration of deferoxamine. To study aluminum speciation after the administration of deferoxamine, high-performance liquid chromatography (HPLC) and ultrafiltration techniques were used. Samples of serum were obtained from six dialysis patients 44 hours after the administration of a single dose of deferoxamine. HPLC and ultrafiltration studies were performed. In the HPLC studies, samples underwent ultrafiltration, the filtrate was injected into the chromatographic system, and detection was performed by UV light and atomic absorption spectrometry. Unknown species of aluminum other than aluminoxamine were found in the early elution fractions. In the ultrafiltration studies, the same samples of serum from the six patients underwent ultrafiltration using membranes with different molecular-weight cutoff values from 1 to 30 kd. The percentages of aluminum found by ultrafiltration using membranes with cutoff values of 5, 10, and 30 kd were greater (64.4% +/- 2.5%, 63.5% +/- 3.7%, and 65.6% +/- 4.3%, respectively) than the percentages obtained with membranes with a 1-kd cutoff value (38.7%), suggesting that the unknown species of aluminum have a molecular weight between 1 and 5 kd. The unknown species of aluminum cannot be aluminoxamine because they behaved in a different way with HPLC.

Aluminum↗

Management of secondary hyperparathyroidism: the gap between diagnosis and treatment. The Renal Osteodystrophy Multicenter Enquiry.

In mild secondary hyperparathyroidism, small daily doses of oral calcitriol represent the physiological form of replacement of this hormone, but in moderate or severe cases, higher doses of calcitriol are needed to suppress parathyroid gland overactivity. Unfortunately, in chronic renal failure, these 2 different forms of calcitriol prescription are not always adequately selected. This review will focus on the current use of calcitriol in renal failure. It includes data from a recent multicenter trial carried out in Spain in which data was gathered from dialysis patients. This trial was designed to determine the current approach to the prevention, diagnosis, and treatment of renal osteodystrophy, with a special emphasis on the gap found between diagnosis and treatment of secondary hyperparathyroidism. Our main goal should be to achieve an adequate and early management of secondary hyperparathyroidism to decrease the number of patients suffering from irreversible enlargement of the parathyroid glands.

Calcitriol↗

Aluminum-induced osteogenesis in osteopenic rats with normal renal function.

Previous studies have shown a different effect of aluminum (Al) on bone metabolism in animals with chronic renal failure and conversely, positive osteogenic effects in animals with normal renal function. The aim of this study was to evaluate the effect of aluminum on bone metabolism in osteopenic rats. We studied male Wistar rats with severe osteopenia induced by adding NH4Cl (2%) to the drinking water over a 6-month period. The rats were divided into two groups and followed for 4 months. The Aluminum group (G1) received AlC13 intraperitoneally (10 mg/kg/5 days/week) (n = 8); the Control group (G2) did not receive any treatment after stopping the administration of NH4Cl (n = 5). In all animals we measured biochemical markers (serum Ca, P, Cr, Al, osteocalcin, hydroxyproline) as well as bone mineral density and bone histomorphometry (BV/TV, CTh, ObS/BS, OTh, and NOc/TV). Bone aluminum content, measured by atomic absorption spectrometry, was 101.6 +/- 13 microg/g in the Al overloaded group and 1.31 +/- 0.14 in controls. Bone mineral density, evaluated by dual X-ray absorptiometry (DXA) at the proximal extremity of the tibia was significantly higher in G1 (0.292 +/- 0.01 g/cm2 versus 0. 267 +/- 0.02 g/cm2). No significant differences were found between the biochemical markers. In the histomorphometric parameters we observed significant differences in G1 compared with G2: an increase in BV/TV (18.59 +/- 5.6 versus 7.69 +/- 3.08%) and in CTh (0.52 +/- 0.06 versus 0.36 +/- 0.07 mm) with a moderate increment of the osteoid thickness (14.05 +/- 4.72 versus 5.25 +/- 0.9 microm) (P < 0. 05). Changes in others parameters and the relationship between biochemical parameters of bone remodeling, Al, and histology were analyzed. These findings indicate that in rats with normal renal function, Al is able to induce bone formation even when osteopenia is present.

Aluminum↗

Low percentage of aluminoxamine and ferrioxamine in uremic serum after desferrioxamine administration.

HPLC was used to study the effectiveness of two different desferrioxamine (DFO) administration strategies (15 mg/kg DFO, 1 h or 44 h before dialysis) on generation of aluminoxamine and ferrioxamine in five hemodialysis patients. The percentage of ultrafilterable aluminum and iron in these patients was also investigated by electrothermal atomic absorption spectrometry. The administration of DFO in both schemes increased the ultrafilterable serum aluminum concentrations from a mean of 17.1 +/- 1.6% to a mean of 75.7 +/- 14.1%. However, 1 h after DFO infusion, only 38.8 +/- 7.7% of the total serum aluminum was bound to DFO; 44 h after DFO infusion, only 15.8 +/- 8.0% was bound. Similar results were obtained for ferrioxamine. These results suggest that the ultrafilterable serum fraction contains aluminum and iron chelated by DFO and by DFO metabolites, which retain similar metal-chelating abilities.

Aluminum↗

Binding of aluminium to plasma proteins: comparative effect of desferrioxamine and deferiprone (L1).

Ultramicrofiltration techniques were used to study both the binding of aluminium to high molecular weight proteins in the presence of different concentrations of desferrioxamine and deferiprone (L1) and the kinetics of aluminium release from human serum proteins. Human serum from healthy volunteers was used in all studies. The serum was spiked with aluminium (100 micrograms/l) and different concentrations of chelators. Ultramicrofiltration was performed with Amicon YMT membranes which had a nominal cut-off of 30,000 Da. Aluminium was measured by graphite furnace atomic absorption spectrometry in total serum and ultrafiltered fluid. Deferiprone shows a higher capability to displace aluminium from serum proteins (80%) than desferrioxamine (60%) at equivalent concentrations of the chelators. The kinetics of the release were also faster for deferiprone, taking 20 min to achieve its maximum effect, whereas, desferrioxamine achieved only 80% of its maximum effect after 2 h. Thus, deferiprone could be an attractive alternative to desferrioxamine, as an aluminium chelator agent.

Aluminum↗

Reconsidering the importance of long-term low-level aluminum exposure in renal failure patients.

Aluminum toxicity is widely considered a problem of the past. However, low-level aluminum exposure and low but abnormal body burdens of aluminum are common. Aluminon, the routinely used histochemical stain for aluminum in bone, has a low sensitivity. The role of aluminum in renal osteodystrophy needs to be reassessed using more sensitive techniques. Low-level aluminum exposure also may resu in subtle neurological dysfunction, another area that needs further investigation.

Aluminum↗